Neural systems for social cognition: gray matter volume abnormalities in boys at high genetic risk of autism symptoms, and a comparison with idiopathic autism spectrum disorder.

Marcia N Goddard,Sophie Van Rijn,Hanna Swaab,Serge A R B Rombouts

doi:10.1007/s00406-015-0623-z

Abstract

Klinefelter syndrome (47, XXY) is associated with several physical, cognitive, and behavioral consequences. In terms of social development, there is an increased risk of autism symptomatology. However, it remains unclear how social deficits are related to abnormal brain development and to what degree underlying mechanisms of social dysfunction in 47, XXY are similar to, or different from, those in idiopathic autism (ASD). This study was aimed at investigating the neural architecture of brain structures related to social information processing in boys with 47, XXY, also in comparison with boys with idiopathic ASD. MRI scans of 16 boys with 47, XXY, 16 with ASD, and 16 nonclinical, male controls were analyzed using voxel-based morphometry (VBM). A region of interest mask containing the superior temporal cortex, amygdala, orbitofrontal cortex (OFC), insular cortex, and medial frontal cortex was used. The Social Responsiveness Scale (SRS) was used to assess degree of autism spectrum symptoms. The 47, XXY group could not be distinguished from the ASD group on mean SRS scores, and their scores were significantly higher than in controls. VBM showed that boys with 47, XXY have significant gray matter volume reductions in the left and right insula, and the left OFC, compared with controls and boys with ASD. Additionally, boys with 47, XXY had significantly less gray matter in the right superior temporal gyrus than controls. These results imply social challenges associated with 47, XXY may be rooted in neural anatomy, and autism symptoms in boys with 47, XXY and boys with ASD might have, at least partially, different underlying etiologies.

Highlights

Klinefelter syndrome (47, XXY) is a genetic condition in which boys have an additional X chromosome, leading to the 47, XXY chromosomal pattern
The main aim of this study was to assess the neural architecture of brain regions associated with social functioning in boys with 47, XXY and boys with autism spectrum disorder (ASD), using voxel-based morphometry
Social Responsiveness Scale (SRS) total scores were available for 14 boys in the control group [MSRS = 23.4 (SD = 12.7)], 13 in the 47, XXY group [MSRS = 73.8 (SD = 25.0)], and 15 in the ASD group [MSRS = 94.2 (SD = 39.5)]

Summary

Introduction

Klinefelter syndrome (47, XXY) is a genetic condition in which boys have an additional X chromosome, leading to the 47, XXY chromosomal pattern. Many studies have focused on the physical, cognitive, and behavioral consequences of 47, XXY [10, 25, 32]. Attention has shifted to the neural basis underlying cognitive and behavioral characteristics of 47, XXY. Structural imaging studies far indicate that compared with nonclinical controls, males with 47, XXY have decreased total brain volume, enlarged ventricles, as well as smaller caudate, cerebellar, temporal, and frontal volumes [26, 27, 30, 37, 46, 57]. Other studies have reported regions of decreased gray matter in the amygdala, insular cortex, hippocampus, cingulate, occipital lobe, parietal lobe, temporal pole, inferior frontal lobe, and superior temporal gyrus (STG) in males with 47, XXY [15, 22, 42, 43, 46]. Functional MRI studies have reported deviant neural activation in the superior

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